13-41065289-T-TAAA

Variant names:

• chr13-41065289-T-TAAA
• rs58699334
• NM_007187.5:c.262+21_262+23dupAAA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000379487.5(WBP4):​c.262+2_262+3insAAA variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0483 in 1,198,040 control chromosomes in the GnomAD database, including 1,262 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (1247 hom., cov: 25)
  • Exomes 𝑓: 0.037 (15 hom.)
• Consequence: WBP4 ENST00000379487.5 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 1 publications found

Genes affected

WBP4 (HGNC:12739): (WW domain binding protein 4) This gene encodes WW domain-containing binding protein 4. The WW domain represents a small and compact globular structure that interacts with proline-rich ligands. This encoded protein is a general spliceosomal protein that may play a role in cross-intron bridging of U1 and U2 snRNPs in the spliceosomal complex A. [provided by RefSeq, Jul 2008]

WBP4 Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with hypotonia, feeding difficulties, facial dysmorphism, and brain abnormalities

  Inheritance: AR Classification: MODERATE Submitted by: G2P

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000379487.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WBP4	NM_007187.5	MANE Select	c.262+21_262+23dupAAA		intron	N/A	NP_009118.1	O75554-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WBP4	ENST00000379487.5	TSL:1 MANE Select	c.262+2_262+3insAAA		splice_region intron	N/A	ENSP00000368801.3	O75554-1
	WBP4	ENST00000953016.1		c.262+2_262+3insAAA		splice_region intron	N/A	ENSP00000623075.1
	WBP4	ENST00000953017.1		c.199+2_199+3insAAA		splice_region intron	N/A	ENSP00000623076.1

Frequencies

GnomAD3 genomes AF: 0.202 AC: 16398 AN: 81294 Hom.: 1247 Cov.: 25

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.186

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.0965

Gnomad SAS AF: 0.104

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.125

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.183

GnomAD2 exomes AF: 0.0104 AC: 357 AN: 34198 AF XY: 0.0106

Gnomad AFR exome AF: 0.0115

Gnomad AMR exome AF: 0.00814

Gnomad ASJ exome AF: 0.0116

Gnomad EAS exome AF: 0.00686

Gnomad FIN exome AF: 0.00282

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.0157

GnomAD4 exome AF: 0.0372 AC: 41521 AN: 1116718 Hom.: 15 Cov.: 0 AF XY: 0.0360 AC XY: 19682 AN XY: 546048

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0193 AC: 474 AN: 24538

American (AMR) AF: 0.0104 AC: 166 AN: 16008

Ashkenazi Jewish (ASJ) AF: 0.0117 AC: 195 AN: 16640

East Asian (EAS) AF: 0.00868 AC: 259 AN: 29844

South Asian (SAS) AF: 0.0171 AC: 898 AN: 52404

European-Finnish (FIN) AF: 0.0215 AC: 535 AN: 24900

Middle Eastern (MID) AF: 0.0138 AC: 46 AN: 3324

European-Non Finnish (NFE) AF: 0.0415 AC: 37527 AN: 903388

Other (OTH) AF: 0.0311 AC: 1421 AN: 45672

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.202 AC: 16397 AN: 81322 Hom.: 1247 Cov.: 25 AF XY: 0.194 AC XY: 7367 AN XY: 37978

African (AFR) AF: 0.155 AC: 3264 AN: 21110

American (AMR) AF: 0.155 AC: 1090 AN: 7018

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 319 AN: 2070

East Asian (EAS) AF: 0.0976 AC: 274 AN: 2806

South Asian (SAS) AF: 0.104 AC: 269 AN: 2598

European-Finnish (FIN) AF: 0.134 AC: 431 AN: 3220

Middle Eastern (MID) AF: 0.113 AC: 12 AN: 106

European-Non Finnish (NFE) AF: 0.256 AC: 10437 AN: 40776

Other (OTH) AF: 0.186 AC: 203 AN: 1090

Alfa AF: 0.0530 Hom.: 98

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.085
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs58699334; hg19: chr13-41639425;